Cell-laden Hydrogel/Titanium Microhybrids: Site-specific cell delivery to metallic implants for improved integration.

Cell-laden Hydrogel/Titanium Microhybrids: Site-specific cell delivery to metallic implants for improved integration.

Acta Biomater. 2016 Jan 20;

Authors: Koenig G, Ozcelik H, Haesler L, Cihova M, Ciftci S, Dupret-Bories A, Debry C, Stelzle M, Lavalle P, Vrana NE

Abstract
Porous titanium implants are widely used in dental, orthopaedic and otorhinolaryngology fields to improve implant integration to host tissue. A possible step further to improve the integration with the host is the incorporation of autologous cells in porous titanium structures via cell-laden hydrogels. Fast gelling hydrogels have advantageous properties for in situ applications such as localisation of specific cells and growth factors at a target area without dispersion. The ability to control the cell types in different regions of an implant is important in applications where the target tissue i) has structural heterogeneity (multiple cell types with a defined spatial configuration with respect to each other); ii) has physical property gradients essential for its function (such as in the case of osteochondral tissue transition). Due to their near immediate gelation, such gels can also be used for site-specific modification of porous titanium structures, particularly for implants which would face different tissues at different locations. Herein, we describe a step by step design of a model system: the model cell-laden gel-containing porous titanium implants in the form of titanium microbead /hydrogel (maleimide-dextran or maleimide-PVA based) microhybrids. These systems enable the determination of the effect of titanium presence on gel properties and encapsulated cell behaviour as a miniaturized version of full-scale implants, providing a system compatible with conventional analysis methods. We used a fibroblast/vascular endothelial cell co-cultures as our model system and by utilizing single microbeads we have quantified the effect of gel microenvironment (degradability, presence of RGD peptides within gel formulation) on cell behaviour and the effect of the titanium presence on cell behaviour and gel formation. Titanium presence slightly changed gel properties without hindering gel formation or affecting cell viability. Cells showed a preference to move toward the titanium beads and fibroblast proliferation was significantly higher in hybrids compared to gel only controls. The MMP (Matrix Metalloproteinase)-sensitive hydrogels induced sprouting by cells in co-culture configuration which was quantified by fluorescent microscopy, confocal microscopy and qRT-PCR (Quantitative Reverse transcription polymerase chain reaction). When the microhybrid up-scaled to 3D thick structures, cellular localisation in specific areas of the 3D titanium structures was achieved, without decreasing overall cell proliferation compared to titanium only scaffolds. Microhybrids of titanium and hydrogels are useful models for deciding the necessary modifications of metallic implants and they can be used as a modelling system for the study of tissue/titanium implant interactions.
STATEMENT OF SIGNIFICANCE: This article demonstrates a method to apply cell-laden hydrogels to porous titanium implants and a model of titanium/hydrogel interaction at micro-level using titanium microbeads. The feasibility of site-specific modification of titanium implants with cell-laden microgels has been demonstrated. Use of titanium microbeads in combination with hydrogels with conventional analysis techniques as described in the article can facilitate the characterization of surface modification of titanium in a relevant model system.

PMID: 26802440 [PubMed - as supplied by publisher]

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[The new eHealth legislation : What lies ahead for hospitals and doctors in private practice?]

[The new eHealth legislation : What lies ahead for hospitals and doctors in private practice?]

HNO. 2016 Jan 22;

Authors: Martenstein I, Wienke A

PMID: 26801892 [PubMed - as supplied by publisher]

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Fronto-temporal branch of facial nerve within the interfascial fat pad: is the interfascial dissection really safe?

Fronto-temporal branch of facial nerve within the interfascial fat pad: is the interfascial dissection really safe?

Acta Neurochir (Wien). 2016 Jan 23;

Authors: Spiriev T, Ebner FH, Hirt B, Shiozawa T, Gleiser C, Tatagiba M, Herlan S

Abstract
BACKGROUND: The study was conducted to clarify the presence or absence of fronto-temporal branches (FTB) of the facial nerve within the interfascial (between the superficial and deep leaflet of the temporalis fascia) fat pad.
METHODS: Eight formalin-fixed cadaveric heads (16 sides) were used in the study. The course of the facial nerve and the FTB was dissected in its individual tissue planes and followed from the stylomastoid foramen to the frontal region.
RESULTS: In the fronto-temporal region, above the zygomatic arch, FTB gives several small twigs running anteriorly in the fat pad above the superficial temporalis fascia and a branch within the temporo-parietal fascia (TPF) to the muscles of the forehead. There were no twigs of the FTB within the interfascial fat pad.
CONCLUSIONS: No branches of the FTB are found in the interfascial (between the superficial and deep leaflet of the temporalis fascia) fat pad. The interfascial dissection can be safely performed without risk of injury to the FTB and potential subsequent frontalis palsy.

PMID: 26801513 [PubMed - as supplied by publisher]

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Management of rhinosinusitis during pregnancy: systematic review and expert panel recommendations.

Management of rhinosinusitis during pregnancy: systematic review and expert panel recommendations.

Rhinology. 2016 Jan 23;

Authors: Lal D, Jategaonkar AA, Borish L, Chambliss LR, Gnagi SH, Hwang PH, Rank MA, Stankiewicz JA, Lund VJ

Abstract
BACKGROUND: Management of rhinosinusitis during pregnancy requires special considerations.
OBJECTIVES: 1. Conduct a systematic literature review for acute and chronic rhinosinusitis (CRS) management during pregnancy. 2. Make evidence-based recommendations.
METHODS: The systematic review was conducted using MEDLINE and EMBASE databases and relevant search terms. Title, abstract and full manuscript review were conducted by two authors independently. A multispecialty panel with expertise in management of Rhinological disorders, Allergy-Immunology, and Obstetrics-Gynecology was invited to review the systematic review. Recommendations were sought on use of following for CRS management during pregnancy: oral corticosteroids; antibiotics; leukotrienes; topical corticosteroid spray/irrigations/drops; aspirin desensitization; elective surgery for CRS with polyps prior to planned pregnancy; vaginal birth versus planned Caesarian for skull base erosions/ prior CSF rhinorrhea.
RESULTS: Eighty-eight manuscripts underwent full review after screening 3052 abstracts. No relevant level 1, 2, or 3 studies were found. Expert panel recommendations for rhinosinusitis management during pregnancy included continuing nasal corticosteroid sprays for CRS maintenance, using pregnancy-safe antibiotics for acute rhinosinusitis and CRS exacerbations, and discontinuing aspirin desensitization for aspirin exacerbated respiratory disease. The manuscript presents detailed recommendations.
CONCLUSIONS: The lack of evidence pertinent to managing rhinosinusitis during pregnancy warrants future trials. Expert recommendations constitute the current best available evidence.

PMID: 26800862 [PubMed - as supplied by publisher]

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Sirtuin 6 modulates hypoxia-induced autophagy in nasal polyp fibroblasts via inhibition of glycolysis.

Sirtuin 6 modulates hypoxia-induced autophagy in nasal polyp fibroblasts via inhibition of glycolysis.

Am J Rhinol Allergy. 2016 Jan 21;

Authors: Shun CT, Lin SK, Hong CY, Lin CF, Liu CM

Abstract
BACKGROUND: To elucidate the interaction between hypoxia-induced autophagy and glycolysis in nasal polyp fibroblasts, and the regulatory role of Sirtuin 6 (SIRT6) in the pathogenesis of nasal polyp.
OBJECTIVE: Through examining the expressions of lactate dehydrogenase (LDH), microtubule-associated protein II light chain 3 (LC3II) (an autophagy marker), and production of lactate under hypoxia, the interaction between autophagy and glycolysis was investigated. The role of SIRT6 on the hypoxia-induced autophagy and glycolysis was also examined.
METHODS: Nasal polyp specimens were used to examine the expressions of hypoxia-inducible factor (HIF) 1 alpha, LDH, and LC3II by Western blot analysis, and primary cultures of nasal polyp fibroblasts were established from resected nasal polyps to measure hypoxia-induced LDH and LC3II expression by Western blot analysis and lactate production by colorimetry. Forced expression of SIRT6 with a lentiviral-based technique was used to evaluate its suppressive effect on autophagy and glycolysis. Immunohistochemical staining was performed to detect the expressions of SIRT6, LDH, and beclin (another autophagy marker) in nasal polyps.
RESULTS: Expression of HIF-1 alpha, LDH, and an autophagy marker, LC3II, are increased in nasal polyp specimens, and forced expression of SIRT6 in nasal polyp fibroblasts inhibited LDH expression, lactate production under hypoxia, and SIRT6. An immunohistochemistry study of nasal polyp showed that SIRT6 expression was reduced and LDH and beclin were enhanced.
CONCLUSION: Analysis of these data indicated that hypoxia may contribute to the formation of nasal polyp by promoting autophagy in nasal polyp fibroblasts. Through the antiglycolytic activity of SIRT6, the autophagy was suppressed, which was beneficial to nasal polyp formation. Modulation of glucose metabolism through SIRT6-based strategy may possess therapeutic potential for nasal polyposis in the future.

PMID: 26803106 [PubMed - as supplied by publisher]

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